Preparation and application of 2,5-difluoropyridine_Industrial additives

Background and overview of preparation and application of 2,5-difluoropyridine

2,5-Difluoropyridine is a starting material for the synthesis of many drugs, especially an important intermediate for many pyridine compounds. For example, 2,5-difluoropyridine can be used to synthesize 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4-hydro-quinolazine-3-carboxylate, 8-chloro -1-Cyclopropyl-7-fluoro-9-methyl-4-oxo-4 polycarbonate-hydroquinolizine-3-carboxylate is an important intermediate for a class of antibacterial drugs.

Preparation and application of 2,5-difluoropyridine

Using 2,5-dichloropyridine as raw material, 2,5-dibromopyridine is prepared by halogenation method, and then through further methylation, the product we want, 2,5-difluoropyridine, can be obtained. The purity of this crude product can meet general reaction requirements and can be directly put into application.

Preparation and application of 2,5-difluoropyridine

CN201610831148.9 provides a preparation method of 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4-hydro-quinolazine-3-carboxylate. The preparation method includes the following steps: step one, react 2,5-difluoropyridine and a chlorine-donating compound in an aprotic solvent to obtain 4-chloro-2,5-difluoropyridine; step two, react 4- Chloro-2,5-difluoropyridine and methyl donor react in an aprotic solvent to obtain 4-chloro-2,5-difluoro-3-methylpyridine; step three, 4-chloro-2 , 5-difluoro-3-methylpyridine reacts with cyclopropaneacetonitrile under the action of a strong base to obtain 2tetrahydrofuran-(4-chloro-5-fluoro-3-methylpyridin-2-yl)-2-cyclopropane Acetonitrile; step four, prepare 2-(4-chloro-5-fluoro-3-methylpyridin-2-yl)-2-cyclopropyl acetaldehyde; step five, prepare 2-(4-chloro-5 -Fluoro-3-methylpyridin-2-yl)-2-cyclopropyl acetaldehyde reacts with malonate diester to obtain 8-chloro-1-cyclopropyl-7-fluoro-9-methyl- 4-Oxo-4hydro-quinolizine-3-carboxylate. The invention can reduce the synthesis steps of the final product and reduce the preparation cost.

References

[1] [Invented in China] CN201410793584.2 Synthesis method of pharmaceutical raw material 2,5-difluoropyridine

[2] CN201610831148.9 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4-hydro-quinolazine-3-carboxylate and preparation method thereof